Estrogen therapy has no long-term effect on cognition in younger postmenopausal women

A randomized clinical trial of estrogen therapy in younger postmenopausal women, aged 50–55, has found no long-term risk or benefit to cognitive function. The National Institutes of Health-supported study, reported in JAMA Internal Medicine on June 24, 2013, looked at women taking conjugated equine estrogens, the most common type of postmenopausal hormone therapy in the United States.

The new findings come from the Women’s Health Initiative Memory Study of Younger Women (WHIMSY) trial and were reported by Mark A. Espeland, Ph.D., Wake Forest School of Medicine, Winston-Salem, N.C., on behalf of the academic research centers involved in the study. The study was funded primarily by the National Institute on Aging (NIA), along with the National Heart, Lung, and Blood Institute (NHLBI), both components of the NIH.

“The WHIMS study found that estrogen-based postmenopausal hormone therapy produced deficits in cognitive function and increased risk for dementia when prescribed to women 65 and older,” said NIA Director Richard J. Hodes, M.D. “Researchers leading the WHIMSY study wanted to expand on those results by exploring the possibility of a window of opportunity whereby hormone therapy might promote or preserve brain health when given to younger women.”

“In contrast to findings in older postmenopausal women, this study tells women that taking these types of estrogen-based hormone therapies for a relatively short period of time in their early postmenopausal years may not put them at increased risk for cognitive decline over the long term,” said Susan Resnick, Ph.D., chief of the Laboratory of Behavioral Neuroscience, in NIA’s Intramural Research Program and a co-author of the study. “Further, it is important to note that we did not find any cognitive benefit after long-term follow-up.”

Neither WHIMSY nor WHIMS was designed to assess the reasons that hormone treatments had different effects on cognition in older and younger postmenopausal women.

WHIMSY is an extension of WHIMS, which was conducted as part of the Women’s Health Initiative (WHI). WHI enrollment took place from 1993–1998 at 40 academic research centers. Participants were randomized to one of two groups: women who had had a hysterectomy received conjugated equine estrogens alone; women with a uterus received estrogens plus a synthetic progestin (medroxyprogesterone acetate). There were companion control groups which received placebos. WHIMSY enrolled 1,326 women who started WHI treatment when they were between 50 and 55 and continued it for an average of seven years. The women were approached to participate in a telephone assessment of cognition an average of seven years after that.

Phone interviews on cognitive function were conducted with 1,168 women. The primary outcome was global cognitive function, which includes measures of memory, problem-solving skills and other cognitive abilities. The researchers also measured specific cognitive functions—verbal memory, attention, executive function, verbal fluency and working memory. The first cognitive assessment was performed when participants’ average age was 67.2 years and the second at an average age of 68.1 years.

The researchers found no meaningful difference in the average global cognitive function scores between women who had been assigned to hormone therapy vs. placebo. This finding applied to women regardless of whether their treatment included the synthetic progestin.

The WHIMSY research team will continue to follow the women in the study with annual telephone interviews to learn whether previous hormone therapy has longer term effects on how cognitive function changes over time. Women considering hormone therapy should consult their physician about how best to treat or prevent menopause symptoms or diseases for which they are at risk.

In addition to NIH support for the study, the hormone therapy used in the WHI hormone trials was provided by Wyeth-Ayerst Laboratories, now part of Pfizer, Inc.

The NIA leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. The Institute’s broad scientific program seeks to understand the nature of aging and to extend the healthy, active years of life. For more information on research, aging, and health, go to www.nia.nih.gov.

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